The precise identify of the T-cell subsets which are largely responsible for the development of corneal allograft rejection is not known. Current opthalmological literature stresses the importance of the cytotoxic T-lymphocyte as a major mediator of corneal immunity. Recently, Loveland and associates have shown that reconstitution of ATXBM (adult thymectomized irradiated and bone marrow reconstituted) mice with Lyt-1+ddeficient (correlating with loss of helper T-cell and delayed type hypersensitivity functions) syngeneic lymphoid cells permits skin allograft survival indenfinitely while reconstitution with-2+ depleted cells (corresponding to loss of cytotoxic T-cell function) leads to graft rejection. Their data implied that it is the Lyt-1+ cell and not the Lyt-2+ cell which is primarily responsible for the development of allograft rejection. The findings of Loveland and associates will be tested in a heterotopic murine corneal transplantation model to test the hypothesis that Lyt-1+ cells also play a central role in corneal allograft rejection. Adult BALB/c (H-2d) mice that will be used as recipients of corneal allografts from C57BL/6 (H-2b) mice will be rendered T-cell deficient by thymectomy and whole body irradiation and then reconstituted of hematopietic elements with anti-Thy-1.2 treated bone marrow cells. Prior to grafting, the ATXBM mice will be selectively reconstituted with either Lyt-1+ depleted or Lyt-2+ depleted syngeneic spleen cells. Donors of the spleen cells will be sensitized with C57BL/6 skin grafts or C57B1/6 heterotopic corneal grafts and intraperitoneal injection of lymphocytes. The corneal allografts will be read and parameters such as loss of clarity, infiltration with inflammatory cells, and vascularization graded on days 7,11,14,21, and 28. The relative frequencies of Lyt-1+ and Lyt=2+ lymphocytes in reconstituted mice will be determined during the 28 day obsevation period and at selected time points thereafter. Confirmation of Loveland's findings for corneal transplants would help to implicate the Lyt-1+ cell as the major mediator of corneal allograft rejection. Identification of the primary effector cell would permit more specific immune modulation in the clinical treatment of corneal allograft rejection. Future studies will include repetition of the experiments using non-sensitized spleen cell donors or congenic recombinant mouse strains as well as further attempts to develop a successful orthotopic murine corneal transplantation model.